PROS1, a clinical prognostic biomarker and tumor suppressor, is associated with immune cell infiltration in breast cancer: A bioinformatics analysis combined with experimental verification

Cell Signal. 2023 Dec:112:110918. doi: 10.1016/j.cellsig.2023.110918. Epub 2023 Oct 10.

Abstract

Background: PROS1 is an encoding gene that can generate protein S. This protein is a glycoprotein found in plasma that conducts physiological functions with vitamin K. However, the impact of its expression remains absent in the progression and prognosis of breast cancer (BC).

Methods: In this study, we comprehensively explored the expression of PROS1 in BC and its relationship with BC patient survival, prognosis, and other clinicopathological features. We investigated how PROS1 influenced the malignant biological behavior of BC cells. A series of enrichment analyses were conducted, and the immune landscape was explored in BC affected by PROS1. We also determined correlations between PROS1 and common drug sensitivities used for BC treatments.

Results: PROS1 had low expression in BC, which tended to result in poor survival of BC patients. Overexpressed PROS1 inhibited the migration and invasion of BC cells as well as the epithelial-mesenchymal transition process by downregulating SNAIL. Functional enrichment analyses revealed that PROS1 was more active in extracellular matrix (ECM) organization and structural constituent, ECM-receptor interaction, and other pathways with its related genes. PROS1 was also found to affect immune activity, including various immune cells infiltrating BC. BC patients with high PROS1 expression tended to have lower IC50 values of three common medications and obtained better efficacy.

Conclusions: PROS1 can become a promising prognostic factor and a possible therapeutic target in BC patients and suppress BC cell metastatic potential. In addition, PROS1 is a crucial factor in immune infiltration in BC.

Keywords: Breast cancer; EMT; Immune infiltrations; PROS1; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Breast Neoplasms* / genetics
  • Computational Biology
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Humans
  • Prognosis
  • Protein S

Substances

  • Biomarkers
  • PROS1 protein, human
  • Protein S